Heart transplantation has become a more and more effective therapeutic strategy in severe heart failure patients. An opportune management of the several medical, immunological and psychological complications, that may occur during heart transplant recipients' life, is mandatory to succeed in this therapeutic approach. Indeed, thanks to heart transplantation, recipients may recover from a lethal cardiovascular disease, but on the other hand, they may encounter several co-morbidities. An optimized management has to involve not only the referring Transplant Center, but also the single patient's personal cardiologist and general physician. Therefore, the present paper has the educational aim to present the most common clinical problems occurring during heart transplant recipients' follow-up, by reviewing current literature in the light of the experience gained by the Bologna Heart Transplant Unit.